Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-20T17:45:49.071Z Has data issue: false hasContentIssue false

Prevention of gentamicin ototoxicity with N-acetylcysteine and vitamin A

Published online by Cambridge University Press:  20 April 2016

I Aladag
Affiliation:
Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
M Guven
Affiliation:
Department of Otorhinolaryngology, Sakarya University Medical Faculty, Sakarya, Turkey
M Songu*
Affiliation:
Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey
*
Address for correspondence: Assoc Prof Murat Songu, Department of Otorhinolaryngology, Izmir Katip Celebi University, Ataturk Training and Research Hospital, Izmir, Turkey Fax: +90 232 243 1530 E-mail: [email protected]

Abstract

Objective:

To investigate the use of systemic N-acetylcysteine and vitamin A in the prevention of gentamicin ototoxicity in rats.

Methods:

Forty-two Wistar rats were divided into four groups according to treatment: intratympanic saline, intratympanic gentamicin, intraperitoneal vitamin A after intratympanic gentamicin, and intraperitoneal N-acetylcysteine after intratympanic gentamicin. Signal-to-noise ratio and distortion product otoacoustic emissions were evaluated in all groups.

Results:

N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 2, 3, 4 and 6 kHz, as determined by the distortion product otoacoustic emission measurements. According to the signal-to-noise measurements, N-acetylcysteine had a significant protective effect at 1.5, 2, 3, 4, 6 and 8 kHz, whilst vitamin A had a significant protective effect at 3, 6 and 8 kHz.

Conclusion:

Gentamicin-induced hearing loss in rats may be prevented by the concomitant use of vitamin A and N-acetylcysteine. Specifically, N-acetylcysteine appeared to have a more protective effect than vitamin A for a greater range of noise frequencies.

Type
Main Articles
Copyright
Copyright © JLO (1984) Limited 2016 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1 Ahmed, RM, Hannigan, IP, MacDougall, HG, Chan, RC, Halmagyi, GM. Gentamicin ototoxicity: a 23-year selected case series of 103 patients. Med J Aust 2012;196:701–4Google Scholar
2 Turnidge, JD, Waterston, JA. Gentamicin and ototoxicity: why this drug is still in use. Med J Aust 2012;196:665–6CrossRefGoogle Scholar
3 Kemp, DT. Stimulated acoustic emissions from within the human auditory system. J Acoust Soc Am 1978;64:1386–91CrossRefGoogle ScholarPubMed
4 Cohen-Kerem, R, Kisilevsky, V, Einarson, TR, Kozer, E, Koren, G, Rutka, JA. Intratympanic gentamicin for Ménière's disease: a meta-analysis. Laryngoscope 2004;114:2085–91CrossRefGoogle ScholarPubMed
5 Salt, AN, Gill, RM, Plontke, SK. Dependence of hearing changes on the dose of intratympanically applied gentamicin: a meta-analysis using mathematical simulations of clinical drug delivery protocols. Laryngoscope 2008;118:1793–800Google Scholar
6 Tepel, M. N-Acetylcysteine in the prevention of ototoxicity. Kidney Int 2007;72:231–2CrossRefGoogle ScholarPubMed
7 Khvoles, R, Freeman, S, Sohmer, H. Transient evoked otoacoustic emissions can be recorded in the rat. Hear Res 1996;97:120–6Google Scholar
8 Khvoles, R, Freeman, S, Sohmer, H. Development of transient evoked otoacoustic emissions in the neonatal rat. Audiol Neurootol 1998;3:4053 Google Scholar
9 Sockalingam, R, Freeman, S, Cherny, TL, Sohmer, H. Effect of high-dose cisplatin on auditory brainstem responses and otoacoustic emissions in laboratory animals. Am J Otol 2000;21:521–7Google ScholarPubMed
10 Hatzopoulos, S, Di Stefano, M, Albertin, A, Martini, A. Evaluation of cisplatin ototoxicity in a rat animal model. Ann N Y Acad Sci 1999;884:211–25CrossRefGoogle Scholar
11 Saliba, I, El Fata, F, Ouelette, V, Robitaille, Y. Are intratympanic injections of N-acetylcysteine and methylprednisolone protective against cisplatin-induced ototoxicity? J Otolaryngol Head Neck Surg 2010;39:236–43Google ScholarPubMed
12 Kubow, S, Woodward, TL, Turner, JD, Nicodemo, A, Long, E, Zhao, X. Lipid peroxidation is associated with the inhibitory action of all-trans-retinoic acid on mammary cell transformation. Anticancer Res 2000;20:843–8Google Scholar
13 Ahn, JH, Kang, HH, Kim, YJ, Chung, JW. Anti-apoptotic role of retinoic acid in the inner ear of noise-exposed mice. Biochem Biophys Res Commun 2005;335:485–90CrossRefGoogle ScholarPubMed
14 Boztepe, OF, Gün, T, Gür, ÖE, Karakuş, MF, Bilal, N, Arda, HN. Effect of N-acetylcysteine for the treatment of otitis media with effusion. J Med Updates 2014;4:20–4Google Scholar
15 Shim, HJ, Kang, HH, Ahn, JH, Chung, JW. Retinoic acid applied after noise exposure can recover the noise-induced hearing loss in mice. Acta Otolaryngol 2009;129:233–8Google Scholar
16 Muurling, T, Stankovic, KM. Metabolomic and network analysis of pharmacotherapies for sensorineural hearing loss. Otol Neurotol 2014;35:16 CrossRefGoogle ScholarPubMed
17 Emmett, SD, West, KP Jr. Gestational vitamin A deficiency: a novel cause of sensorineural hearing loss in the developing world? Med Hypotheses 2014;82:610 CrossRefGoogle ScholarPubMed
18 Hammer, Ø, Harper, DA, Ryan, PD. PAST: paleontological statistics software package for education and data analysis. Palaeontol Electron 2001;4:9 Google Scholar
19 Cheng, AG, Cunningham, LL, Rubel, EW. Mechanisms of hair cell death and protection. Curr Opin Otolaryngol Head Neck Surg 2005;13:343–8Google Scholar
20 Miman, MC, Ozturan, O, Iraz, M, Erdem, T, Olmez, E. Amikacin ototoxicity enhanced by Ginkgo biloba extract (EGb 761). Hear Res 2002;169:121–9Google Scholar
21 Feghali, JG, Liu, W, Van Der Water, TR. L-N-Acetyl-cysteine protection against cisplatin-induced auditory neuronal and hair cell toxicity. Laryngoscope 2001;111:1147–55CrossRefGoogle ScholarPubMed
22 Weinbroum, A, Rudick, V, Ben-Abraham, R, Karchevski, E. N-acetyl-L-cysteine for preventing lung reperfusion injury after liver ischemia-reperfusion: a possible dual protective mechanism in a dose-response study. Transplantation 2000;69:853–9Google Scholar
23 Mazzon, E, Britti, D, De Sarro, A, Caputi, AP, Cuzzocrea, S. Effect of N-acetylcysteine on gentamicin-mediated nephropathy in rats. Eur J Pharmacol 2001;424:7583 CrossRefGoogle ScholarPubMed
24 Damodaran, S, Parkin, KL, Fennema, OR, eds. Fennema's Food Chemistry, 4th edn. Boca Raton, Florida: CRC Press, 2008 Google Scholar
25 Lopez-Gonzalez, MA, Guerrero, JM, Rojas, F, Delgado, F. Ototoxicity caused by cisplatin is ameliorated by melatonin and other antioxidants. J Pineal Res 2000;28:7380 Google Scholar
26 Hyppolito, MA, de Oliveira, JA, Rossato, M, Holanda, F. Cisplatin ototoxicity and otoprotector to cilliated cells by ginkgo biloba extract: anatomic and electrophysiologic study [in Portuguese]. Rev Bras Otorrinolaringol 2003;69:504–11CrossRefGoogle Scholar
27 McAlpine, D, Johnstone, BM. The ototoxic mechanism of cisplatin. Hear Res 1990;47:191204 CrossRefGoogle ScholarPubMed